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dc.contributor.authorMishra, Parul
dc.contributor.authorFlynn, Julia
dc.contributor.authorStarr, Tyler N.
dc.contributor.authorBolon, Daniel N.
dc.date2022-08-11T08:09:45.000
dc.date.accessioned2022-08-23T16:42:16Z
dc.date.available2022-08-23T16:42:16Z
dc.date.issued2016-04-19
dc.date.submitted2016-10-05
dc.identifier.citationCell Rep. 2016 Apr 19;15(3):588-98. doi: 10.1016/j.celrep.2016.03.046. Epub 2016 Apr 7. <a href="http://dx.doi.org/10.1016/j.celrep.2016.03.046">Link to article on publisher's site</a>
dc.identifier.issn2211-1247 (Electronic)
dc.identifier.doi10.1016/j.celrep.2016.03.046
dc.identifier.pmid27068472
dc.identifier.urihttp://hdl.handle.net/20.500.14038/40056
dc.description.abstractTo probe the mechanism of the Hsp90 chaperone that is required for the maturation of many signaling proteins in eukaryotes, we analyzed the effects of all individual amino acid changes in the ATPase domain on yeast growth rate. The sensitivity of a position to mutation was strongly influenced by proximity to the phosphates of ATP, indicating that ATPase-driven conformational changes impose stringent physical constraints on Hsp90. To investigate how these constraints may vary for different clients, we performed biochemical analyses on a panel of Hsp90 mutants spanning the full range of observed fitness effects. We observed distinct effects of nine Hsp90 mutations on activation of v-src and glucocorticoid receptor (GR), indicating that different chaperone mechanisms can be utilized for these clients. These results provide a detailed guide for understanding Hsp90 mechanism and highlight the potential for inhibitors of Hsp90 that target a subset of clients.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=27068472&dopt=Abstract">Link to Article in PubMed</a>
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectBiochemistry
dc.subjectMolecular Biology
dc.titleSystematic Mutant Analyses Elucidate General and Client-Specific Aspects of Hsp90 Function
dc.typeJournal Article
dc.source.journaltitleCell reports
dc.source.volume15
dc.source.issue3
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3865&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/2860
dc.identifier.contextkey9233079
refterms.dateFOA2022-08-23T16:42:16Z
html.description.abstract<p>To probe the mechanism of the Hsp90 chaperone that is required for the maturation of many signaling proteins in eukaryotes, we analyzed the effects of all individual amino acid changes in the ATPase domain on yeast growth rate. The sensitivity of a position to mutation was strongly influenced by proximity to the phosphates of ATP, indicating that ATPase-driven conformational changes impose stringent physical constraints on Hsp90. To investigate how these constraints may vary for different clients, we performed biochemical analyses on a panel of Hsp90 mutants spanning the full range of observed fitness effects. We observed distinct effects of nine Hsp90 mutations on activation of v-src and glucocorticoid receptor (GR), indicating that different chaperone mechanisms can be utilized for these clients. These results provide a detailed guide for understanding Hsp90 mechanism and highlight the potential for inhibitors of Hsp90 that target a subset of clients.</p>
dc.identifier.submissionpathoapubs/2860
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology
dc.source.pages588-98


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